Effect of Pleiotrophin in Neural Transplantation

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  • Hida Hideki
    Department of Neurophysiology & Brain Science, Nagoya City University Graduate School of Medical Sciences

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  • 神経細胞移植におけるプレイオトロフィンの効果

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Abstract

Before clinical applications of neural stem/progenitor cells in neural transplantation, many basic problems need investigating; for example, how to induce the differentiation to neurons and how to improve the survival of grafted cells. Therefore, search and analysis for differentiation/survival factors are important areas of neural transplantation research. To for search differentiation/survival factors of dopaminergic (DAergic) neurons, we investigated enhanced trophic factor in the DA-depleted striatum using ELISA and a cDNA microarray. Expression of pleiotrophin (PTN), VEGF and GDNF were enhanced in the DA-depleted striatum. To ascertain the effect of PTN on survival and differentiation of DAergic neurons, cultured DAergic neurons from E15 ventral mesencephalon and ES-derived nestin positive cells were treated with PTN. Cultured DAergic neurons treated with PTN (50ng/ml) at 1 and 3day in vitro increased the number of TH-positive cells at 5day in vitro, although treatment with midkine (50ng/ml), a family protein, did not; indicating that PTN promoted survival specific to DAergic neurons. It was found that PTN treatment to ES-derived nestin positive cells increased the number of TH-positive cells after neural differentiation, showing that PTN promoted differentiation to DAergic neurons from neural stem cells. To ascertain the effect of PTN in neural transplantation, donor cells (E15 ventral mesencephalic tissue) were treated with PTN during cell preparation; cells were transplanted into the striatum of rat hemiparkinson model and methamphetamine-induced rotation testing was carried out until 5 weeks after transplantation. It was found that PTN treatment during cell preparation improved motor functional behavior as compared to controls, and that there were more surviving DAergic neurons in the striatum at 5 weeks after transplantation in ther PTN-treated group. The results showed that PTN treatment of donor cells promotes the recovery of disturbed motor function. Our data indicates that PTN, an enhanced trophic factor in DA-depleted striatum, is useful as a differentiation/survival factor for DAergic neurons in neural transplantation.

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